title: Identification of pleiotropic genetic effects on obesity and brain anatomy.
abstract: OBJECTIVE
  Obesity is a major contributor to the global burden of chronic disease and disability, though current knowledge of causal biologic underpinnings is lacking. Through the regulation of energy homeostasis and interactions with adiposity and gut signals, the brain is thought to play a significant role in the development of this disorder. While neuroanatomical variation has been associated with obesity, it is unclear if this relationship is influenced by common genetic mechanisms. In this study, we sought genetic components that influence both brain anatomy and body mass index (BMI) to provide further insight into the role of the brain in energy homeostasis and obesity.
  
  
  METHODS
  MRI images of brain anatomy were acquired in 839 Mexican American individuals from large extended pedigrees. Bivariate linkage and quantitative analyses were performed in SOLAR.
  
  
  RESULTS
  Genetic factors associated with an increased BMI were also associated with a reduced cortical surface area and subcortical volume. We identified two genome-wide quantitative trait loci that influenced BMI and the ventral diencephalon volume, and BMI and the supramarginal gyrus surface area, respectively.
  
  
  CONCLUSIONS
  This study represents the first genetic analysis seeking evidence of pleiotropic effects acting on both brain anatomy and BMI. Our results suggest that a region on chromosome 17 contributes to the development of obesity, potentially through leptin-induced signaling in the hypothalamus, and that a region on chromosome 3 appears to jointly influence the food-related reward circuitry and the supramarginal gyrus.
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, Tex., USA.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Curran
authors.forename: D Reese
authors.initials: DR
authors.lastname: McKay
authors.forename: Anderson M
authors.initials: AM
authors.lastname: Winkler
authors.forename: Rene L
authors.initials: RL
authors.lastname: Olvera
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Carless
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Dyer
authors.forename: Jack W
authors.initials: JW
authors.lastname: Kent
authors.forename: Peter
authors.initials: P
authors.lastname: Kochunov
authors.forename: Emma
authors.initials: E
authors.lastname: Sprooten
authors.forename: Emma E
authors.initials: EE
authors.lastname: Knowles
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Comuzzie
authors.forename: Peter T
authors.initials: PT
authors.lastname: Fox
authors.forename: Laura
authors.initials: L
authors.lastname: Almasy
authors.forename: Ravindranath
authors.initials: R
authors.lastname: Duggirala
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.forename: David C
authors.initials: DC
authors.lastname: Glahn
mesh_terms: D000328:Adult; D015992:Body Mass Index; D001921:Brain / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology; D058068:Endophenotypes; D005260:Female; D008040:Genetic Linkage; D058685:Genetic Pleiotropy; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D008297:Male; D009765:Obesity / Q000235:genetics* / Q000473:pathology*